PHA/NHLBI K08/K23 Award Winner 2006

Paul B. Yu, MD, PhD Paul B. Yu, MD, PhD

Massachusetts General Hospital
“The Role of the BMP Type II Receptor in Vascular Function”
NHLBI Mentored Clinical Scientist Development Award (K08)
July 1, 2006 – June 30, 2011

Summary of Research Project:

The Role of the BMP Type II Receptor in Vascular Function

Pulmonary hypertension is thought to originate in part from abnormal growth or maintenance of cells of the pulmonary vessels. Pulmonary vascular remodeling as such may lead to profound debilitation, right ventricular heart failure, the need for lung and/or heart transplantation, or death. A relatively recent development in this field was the identification of mutations in a single gene locus, the bone morphogenetic protein type II receptor (BMPR-II), in families with an inherited form of pulmonary hypertension. A major research effort is underway to understand the role of this receptor in pulmonary vascular development and maintenance, and its role in the disease of these afflicted families and in pulmonary hypertension in general. Our research has focused on a small animal model constructed to recapitulate the types of genetic mutations found in humans with the familial form of the disease. We have found that pulmonary vascular cells obtained from mice with BMPR-II mutations exhibit unexpected abnormalities in signaling. These abnormalities in signaling appear to lead to abnormal control of cell growth and differentiation in these cell types, and may contribute to the abnormal remodeling that leads to lesions of abnormally growing smooth muscle and endothelial cell types in diseased lung vessels. It is hoped that we can correlate these findings with a model of pulmonary hypertension in these same mutant mice. These cellular and animal models will help determine the precise pathways by which BMPR-II receptors and their signals affect the growth and developmental plan of pulmonary vessels. Understanding the role of BMPR-II in initiating disease could provide potential strategies for intercepting the disease or stopping its progression, and could provide a platform for testing these strategies.

Curriculum Vitae

  • 09/1988-05/1992 B.S. in Biology Stanford University, Stanford, CA
  • 09/1988-12/1994 A.B. in Philosophy Stanford University, Stanford, CA
  • 08/1992-05/1999 M.D., School of Medicine Duke University, Durham, NC
  • 08/1996-08/2000 Ph.D., Department of Immunology Duke University, Durham, NC

Postdoctoral Training

Internship and Residencies:

  • 06/1999-06/2001 Internship and Residency, Internal Medicine University of California at San Francisco, CA

Fellowship:

  • 07/2001-06/2005 Clinical and Research Fellow in Medicine Massachusetts General Hospital, Boston, MA Research Fellow in Medicine Harvard Medical School, Boston, MA

Licensure and Certification

  • 06/1999-06/2001 Limited License, State of California
  • 01/2003-present Medical License, State of Massachusetts
  • 11/2003 Board Certification in Internal Medicine, American Board of Internal Medicine

Hospital Appointments

  • 01/2003-present Consultant in Cardiology Cape Cod Hospital, Hyannis, MA
  • 07/2005-06/2006 Graduate Assistant in Medicine Massachusetts General Hospital, Boston, MA
  • 07/2006- Assistant in Medicine Massachusetts General Hospital, Boston, MA

Academic Appointments

  • 04/1/2006- Instructor in Medicine Harvard Medical School, Boston, MA

Major Committee Assignments

Medical School:

  • 09/1996-05/1997 Medical School Admissions Committee Duke University, Durham, NC Executive Committee Member

Professional Societies

  • 09/1995-09/1996 Asian Pacific American Medical Students Association Local Chapter Vice President, and Southeast Regional Representative
  • 01/2000-present Member, American Medical Association

Community Service

  • 08/1994-05/1998 Youth Mentor, tutoring and mentoring for Durham middle school students Duke University Volunteers in Youth Program

Awards

  • 09/1995-08/1996 Howard Hughes Medical Institute Research Training Fellowship
  • 07/2005-06/2007 GlaxoSmithKline Research and Education Foundation for Cardiovascular Disease International Competitive Grants Award for Young Investigator
  • 07/2006-06/2011 Pulmonary Hypertension Association Mentored Clinical Scientist Award
  • 09/2006 Best Oral Abstract Presentation Award, Massachusetts General Hospital Cardiovascular Research Center Annual Retreat
  • 11/2006 American Heart Association Cardiopulmonary Resuscitation and Critical Care Travel Award

Other Published Articles

  • Yu PB, Beppu H, Kawai N, Li E, Bloch KD. “Pulmonary artery smooth muscle cells deficient in bone morphogenetic protein type II receptor exhibit ligand-specific gain of signaling function,” Journal of Biological Chemistry, 2005; 280(26):24443.
  • Beppu H, Ichinose F, Kawai N, Jones RC, Yu PB, Zapol WM, Miyazono K, Li E, and Bloch KD. “Heterozygous mutation of the BMP type II receptor gene causes pulmonary hypertension in mice,” Am J Physiol Lung Cell Mol Physiol, 2004; 287(6):1241
  • Yu PB, Beppu H, Kawai N, Ichinose F, Bloch KD, Li E. “Pulmonary Artery Smooth Muscle Cells Deficient in Type II Bone Morphogenetic Protein Receptor Exhibit Gain of Function in Response to Bone Morphogenetic Protein 7.” Oral abstract, American Hearth Association Scientific Sessions, New Orleans, November 2004. 

 

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